The present invention is directed to the reduction of protein deposition on surfaces. The invention provides compositions and methods for inhibiting the deposition of protein on the surfaces of medical devices, particularly biomedical and prosthetic devices. The invention is based on the discovery that certain polymers and related copolymers comprising the monomer n-isopropylacrylamide (NIPAM) significantly inhibit protein deposition on the surfaces of contact lenses.
Proteins adsorb to almost all surfaces and the minimization or elimination of protein adsorption has been the subject of numerous studies, such as those reported by Lee, et al., in J. Biomed. Materials Res., vol. 23, pages 351-368 (1989). Sensors, chromatographic supports, immunoassays, membranes for separation, biomedical implants, prosthetic devices (e.g., contact lenses) and many other devices or objects can be adversely affected by protein adsorption. A method and/or means for treating the surfaces of such objects so as to prevent or reduce protein deposition would therefore be quite advantageous.
The use of NIPAM-containing polymers to modify surfaces and control protein deposition on glass and silicon substrates has been previously described. The following publications provide further background regarding such modifications:
1. Kidoki, et al., Langmuir, 17, pp. 2402-2407 (2001);
2. Bohanon, et al., J. Biomater. Sci. Polymer Edn., Vol. 8, No. 1, pp. 19-39 (1996);
3. International (PCT) Patent Publication No. WO 02/30571 A2 (Sudor);
4. U.S. Pat. No. 6,447,897 (Liang, et al.);
5. U.S. Pat. No. 6,270,903 (Feng, et al.); and 6. Huber, et al., Science, Vol. 301, pp. 352-354, Jul. 18, 2003.
The above-identified publications do not disclose or suggest that NIPAM-containing polymers could be used to modify the surfaces of medical devices, such as contact lenses, and to control protein deposition and release on such surfaces.
The terms “soft” and “hard” relative to contact lenses are generally associated with not only the relative hardness of the respective types of lenses, but also the type of polymeric material from which the lenses are formed. The term “soft” generally denotes a contact lens that is formed from a hydrophilic polymeric material, such as hydroxyethyl methacrylate or “HEMA”, while the term “hard” generally denotes a lens that is formed from a hydrophobic polymeric material, such as polymethylmethacrylate or “PMMA”. The surface chemistry and porosity of the hard and soft lenses is quite different. Soft lenses typically contain a large amount of water, are quite porous, and bear ionic charges on the exposed surfaces of the lenses, while hard lenses are considerably less porous and generally do not bear ionic surface charges.
The ionic surfaces and porous nature of soft contact lenses can lead to significant problems when the lenses come into contact with the tear film due to the complex composition of the tear film, which is largely comprised of proteins, lipids, enzymes and various electrolytes. Tear components include albumin, lactoferrin, lysozyme and a number of immunoglobulins. The uptake of proteins from the tear fluid onto the lens is a common problem and depends on a number of factors, including the nature of the materials from which the lens is made.
Soft contact lenses act as efficient substrates for protein deposition and adsorption. This fouling can lead to dehydration of the lens and instability of the tear film, resulting in discomfort and lack of tolerance in the wearer. Adsorption of proteins can also facilitate bacterial colonization and this can increase the risk of vision-threatening infections.
In view of the potential fouling of contact lenses and the problems created by such fouling, as discussed above, it is generally accepted that contact lens cleaning must be a regular part of a patient's lens care regimen. Many different types of cleaning agents have been utilized in the past for this purpose. Cleaning agents such as surfactants and enzymes are typically incorporated into contact lens care products to remove protein deposits. However, the use of these agents can lead to irritation, and in cases where rubbing and cleaning regimens are required, there is a possibility that the cleaning agents will not be used properly or will be used in a manner that damages the lenses. In view of the foregoing problems, it would be advantageous if the surfaces of contact lenses could be modified so as to prevent or reduce the adsorption of proteins to the surfaces.
Various attempts have been made to reduce protein deposit formation on contact lenses. The following patents may be referred to for further background regarding such attempts:
U.S. Pat. No. 4,411,932 describes the use of polymeric alcohols and polymeric ethers, including poly(ethylene glycol), polyethylene oxide and polyethylene glycol methyl ether, as prophylactic agents against soilant deposits on contact lenses;
U.S. Pat. No. 6,274,133 (Hu et al.) describes the use of cationic cellulose polymers to prevent the build-up of lipids and proteins on a silicone-hydrogel lens;
U.S. Pat. No. 6,323,165 (Heiler, et al.) describes the use of charged polyquaternium polymers to block the binding of proteins to hydrophilic contact lenses; and
U.S. Pat. No. 6,096,138 (Heiler, et al.) describes the use of polyquaternium polymers such as Luviquat® (BASF), which is a mixture of vinylpyrrolidone and vinylimidazolium moieties that can bind to hydrophilic contact lens materials, so as to block the binding of proteinaceous materials to the lenses.
These prior attempts to reduce protein binding have drawbacks. For example, cationic polymers may act as irritants upon contact with the eye when utilized at high concentrations. Additionally, due to the positive charge character of these macromolecules, complex formation with anionic surfactants or other components of CLC products may lead to flocculation and phase separation in the formulation, which is a significant problem. Accordingly, there is need for new approaches to provide protein resistant surfaces.
Due to the trend toward use of extended wear lenses, it would be useful to be able to provide contact lens wearers with a contact lens surface that inhibits adsorption of proteinaceous matter for extended time periods, without compromising the safety of the patient. The polymer should also be compatible in contact lens care solutions when storage, disinfection and/or cleaning are desired by the patient. The present invention is directed to satisfying these needs.